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In vitro clinical-grade generation of red blood cells from human umbilical cord blood CD34+ cells

Authors

  • Eun Jung Baek,

    1. From the Department of Laboratory Medicine and the Brain Korea 21 Project for Medical Science, Yonsei University College of Medicine, and the Department of Laboratory Medicine, Hanyang University College of Medicine, Seoul, Korea.
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  • Han-Soo Kim,

    1. From the Department of Laboratory Medicine and the Brain Korea 21 Project for Medical Science, Yonsei University College of Medicine, and the Department of Laboratory Medicine, Hanyang University College of Medicine, Seoul, Korea.
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  • Sinyoung Kim,

    1. From the Department of Laboratory Medicine and the Brain Korea 21 Project for Medical Science, Yonsei University College of Medicine, and the Department of Laboratory Medicine, Hanyang University College of Medicine, Seoul, Korea.
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  • Honglien Jin,

    1. From the Department of Laboratory Medicine and the Brain Korea 21 Project for Medical Science, Yonsei University College of Medicine, and the Department of Laboratory Medicine, Hanyang University College of Medicine, Seoul, Korea.
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  • Tae-Yeal Choi,

    1. From the Department of Laboratory Medicine and the Brain Korea 21 Project for Medical Science, Yonsei University College of Medicine, and the Department of Laboratory Medicine, Hanyang University College of Medicine, Seoul, Korea.
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  • Hyun Ok Kim

    1. From the Department of Laboratory Medicine and the Brain Korea 21 Project for Medical Science, Yonsei University College of Medicine, and the Department of Laboratory Medicine, Hanyang University College of Medicine, Seoul, Korea.
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  • This work was supported by the Korea Research Foundation (Grant KRF-2007-313-E00445) funded by the Korean government (MOEHRD).

Hyun Ok Kim, MD, PhD, Department of Laboratory Medicine, Yonsei University College of Medicine, CPO Box 8044, 134 Sinchon-dong, Seodaemun-gu, Seoul, Korea; e-mail: hyunok1019@yuhs.ac

Abstract

BACKGROUND: There is no appropriate alternative source of red blood cells (RBCs) to relieve the worsening shortage of blood available for transfusion. Therefore, in vitro generation of clinically available RBCs from hematopoietic stem cells could be a promising new source to supplement the blood supply. However, there have been few studies about the generation of clinical-grade RBCs by coculture on human mesenchymal stem cells (MSCs) and various cytokine supplements, even though the production of pure RBCs requires coculture on stromal cells and proper cytokine supplements.

STUDY DESIGN AND METHODS: Umbilical cord blood (CB) CD34+ cells were cultured in serum-free medium supplemented with two cytokine sets of stem cell factor (SCF) plus interleukin-3 (IL-3) plus erythropoietin (EPO) and SCF plus IL-3 plus EPO plus thrombopoietin (TPO) plus Flt-3 for 1 week, followed by coculture upon MSCs derived from bone marrow (BM) or CB for 2 weeks.

RESULTS: Almost pure clinical-grade RBCs could be generated by coculturing with CB-MSCs but not BM-MSCs. Expansion fold and enucleation rate were significantly higher in coculture with CB-MSCs than BM-MSCs. Despite a 2.5-fold expansion of erythroblasts in the presence of TPO and Flt-3 for 8 days, the final RBC count was higher without TPO and Flt-3.

CONCLUSIONS: This study is the first report on generating clinical-grade RBCs by in vitro culture with human MSCs and compared effectiveness of several cytokines for RBC production. This provides a useful basis for future production of clinically available RBCs and a model of erythropoiesis that is analogous to the in vivo system.

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